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'HE DEVELOPMENT OF THE SYMPATHETIC 
NERVOUS SYSTEM IN MAMMALS 



Bt 
ALBERT KUNTZ 

7 



With Eighteen Figures 



A Dissertation Submitted to the Faculty of the Graduate College of the State 

University of Iowa in partial fulfillment of the requirements 

for the Degree of Doctor of Philosophy. 



Reprinted from the 

jottrnal of comparative netrroloqy and pstcholost 

Vol. M, No. 3, June, 1910. 



1 









THE DEVELOPMENT OF THE SYMPATHETIC 
NERVOUS SYSTEM IN MAMMALS 

ALBERT KUNTZ 

From the Laboratories of Animal Biology of the State University of Iowa 

WITH EIGHTEEN FIGURES 

CONTENTS 

I.f Introduction. ; 213 

II. Historical Survey 214 

III. Methods of Investigation 218 

IV. Observations 219 

1 . Sympathetic trunks 219 

a. Early development 219 

h. Cell migration 222 

c. Later development 229 

d. Nature of migrating cells 230 

2 . Prevertebral plexuses 233 

a. Develo ment 233 

h. Histogenetic relationships 234 

3. Vagal sympathetic plexuses 235 

a. Introductory 235 

6. Myenteric and submucous plexuses 236 

c. Pulmonary plexuses 239 

d. Cardiac plexus 239 

e. Cell migration along the vagi 241 

V. Discussion of Results, and Conclusions 246 

a. Migration of medullary cells 246 

6. The neurilemma 248 

c. Sympathetic excitatory and sympathetic sensory neurones 249 

d. A wider application of Schaper's conception 351 

e. Relation of the sympathetic to the central nervous system 251 

/. Functional relations 252 

VI. Summary 253 

Bibliography 256 



i 



212 ALBERT KUNTZ 

I. INTRODUCTION 

The present investigation of the development of the s^anpa- 
thetic nervous system in mammals was carried on in the labora- 
tories of Animal Biology of the State University of Iowa, under the 
direction of Prof. Gilbert L. Houser. 

Although much excellent work has been done on the develop- 
ment of the sympathetic nervous system, om' knowledge concern- 
ing the sympathetic neurones and the relation of the sympathetic 
to the central nervous system is still very meager. Our newer 
conceptions of nerve-components and of the functional divisions 
of the peripheral nervous system call for a re-investigation of the 
development of the s;^Tiipathetic system in order to brhig this 
division of the nervous system into harmonj^ with estabhshed 
facts. 

The present investigation was undertaken in order to further 
exact knowledge concerning the histogenesis of the s}^npathetic 
system, to establish the histogenetic relationships between the 
sympathetic neurones and the neurones in the central nervous 
S3^stem, and to correlate the s^Tupathetic s^^stem with the other 
functional divisions of the nervous system. The most important 
results achieved pertain to increased knowledge concerning the 
histogenesis of the sympathetic S3^stem and its relation to the 
central nervous system, and to the fact that the cardiac plexus 
and the s}Tiipathetic plexuses in the walls of the ^dsceral organs 
are not derived from the s^onpathetic trunks, as has hitherto 
been supposed, but have then* origin in nervous elements which 
migrate from the vagus gangha and the walls of the hind-brain 
along the fibers of the vagi. During the progress of the work, two 
prelhiiinary papers were pubhshed (see BibHography) . 

It is a real pleasure to express my deep sense of obHgation to 
Prof. Houser for his many helpful suggestions and for the inspira- 
tion afforded by the constant enthusiastic interest manifested by 
him during the progress of this investigation. I desire also to 
express my indebtedness to Dr. F. A. Stromsten for many valua- 
ble suggestions in technique. 



LIBRARY OF CONGRESS 

RECEIVED 

COT 2...]924 

*■ - « 

\ DOCUMENTS PlV(StON 



SYMPATHETIC SYSTEM IN MAMMALS 213 

II. HISTORICAL SURVEY 

The earliest observations on development of the sympathetic 
nervous system are those of Remak ('47). That pioneer among 
the investigators of the sympathetic system described the anlagen 
of the sympathetic trunks in the chick as ganglionic enlargements 
on the communicating rami, situated at their point of deviation 
from the spinal nerves. He believed that the cells composing 
these ganglionic enlargements are derived from preformed ele- 
ments arising in the mesoderm. This view of the mesodermal 
origin of the sympathetic nervous system held undisputed sway 
for more than two decades, and has found advocates, among 
whom may be mentioned Paterson ('91), in more recent times. 

The work of Balfour ('77) marks the beginning of our modern 
conception of the ectodermal origin of the sympathetic nervous 
system. According to his observations on the selachians, the 
anlagen of the sympathetic trunks arise as simple enlargements on 
the spinal nerve-trunks. Subsequently, these enlargements ad- 
vance toward the aorta, each, however, retaining connection with 
its respective nerve by a fibrous branch which becomes the com- 
municating ramus. These ganglionic enlargements are at first 
independent of each other, but become united later by longitudinal 
commissures. These observations on the selachians were sub- 
stantiated by Onodi ('86), Van Wijhe ('89), and Hoffmann ('99). 

Schenck and Birdsall ('78) extended the conception of Balfour, 
somewhat modified, to the higher vertebrates. Tracing the devel- 
opment of the sympathetic trunks in birds and mammals, they 
found that before the anlagen of the sympathetic trunks appear, 
the spinal ganglia are not sharply limited distally. Groups of 
cells become detached from the distal ends of the spinal ganglia 
and advance far into the spinal nerve-trunks. These cells, they 
believe, constitute the anlagen of the sympathetic trunks, but 
they have given no clear conception of the process by which these 
cells are transferred from the spinal ganglia to their new location 
in the sympathetic anlagen. 

Kolliker ('97) adopted the doctrine of Balfour and attempted 
to extend it to the peripheral sympathetic plexuses. In the ab- 

THE JOURNAL OF COMPARATIVE NEUROLOGY AND PSTCHOLOGY, VOL. 20, NO. 3 



216 ALBERT KUNTZ 

Kohn ('05, '07) describes the anlagen of the sympathetic trunks 
in the rabbit as a pair of columns of cell-aggregates arising along 
the sides of the dorsal surface of the aorta. Similar cells are found 
in intermediate positions between these cell-aggregates and the 
spinal nerves, in the paths later occupied by the fibers of the com- 
municating rami. According to Kohn, the sympathetic anlagen 
are composed of cells which arise by the division of elements which 
have not migrated thither, but were differentiated in situ in 
the spinal nerves. Embryonal neurocytes deviate from the 
course of the spinal nerves toward the aorta. By division 
they yield a syncytial cellular communicating ramus which 
extends toward the aorta. Cell-groups become separated from 
its distal end and give rise to the cell-aggregates of the sympa- 
thetic anlagen. 

According to Neumayer's observations on embryos of Lacerta 
(spec?) and the chick ('06), the anlagen of the sympathetic trunks 
arise as short cellular outgrowths on the spinal nerves which early 
develop ganglionic enlargements at their distal ends, which become 
united later by longitudinal cellular commissures. Neumayer, 
like Kohn, traces the origin of the sympathetic system directly 
to the spinal nerves. He is of the opinion that in all vertebrates 
the sjrmpathetic anlagen arise from cells which are to be regarded 
as the offspring of the dorsal and the ventral nerve-roots and are 
differentiated in situ, like the cells of the spinal ganglia and the 
fibers of the nerve-roots. 

The work of Froriep ('07) on embryos of Torpedo and of the 
rabbit, marks a decided advance in our knowledge of the histo- 
genesis of the sympathetic nervous system. He succeeded in 
tracing medullary cells peripherally along the ventral roots of 
the spinal nerves. These cells he formerly interpreted as elements 
which give rise to the neurilemma. After Harrison ('04) showed 
experimentally that in amphibians the cells giving rise to the neu- 
rilemma of both the sensory and the motor fibers have their origin 
in the neural crest, Froriep concluded that the cells migrating 
peripherally in the ventral nerve-roots, either alone or with cells 
which wander out from the spinal ganglia, give rise to the sym- 
pathetic nervous system. In his summary he expresses the opin- 



SYMPATHETIC SYSTEM IN MAMMALS 217 

ion that all the sympathetic neurones in the sympathetic trunks 
as well as in the prevertebral and the peripheral sympathetic 
plexuses have their origin in the ventral half of the neural tube. 

Held ('09) and Marcus ('09) have recently taken exception to 
Froriep's conclusions. Held has attempted to show, for the entire 
vertebrate series, that the cells present in the motor nerve-roots 
play no part in the development of the sympathetic system. He 
still regards the sympathetic system as an offshoot from the spinal 
ganglia. Marcus has attempted to show that the cell-groups 
which Froriep observed in the ventral roots of the spinal nerves 
do not wander out from the neural tube, but migrate thither from 
the neural crest. In early stages of embryos of Torpedo, he has 
observed cell-chains connecting the neural crest with the cell- 
aggregates in the ventral nerve-roots. He concludes, therefore, 
that the neural crest represents the sole source of all the cells 
giving rise to sympathetic neurones. 

This brief review of the literature has shown that the advocates 
of the theory of the ectodermal origin of the sympathetic nervous 
system agree in tracing the origin of the cells giving rise to the 
sympathetic anlagen to the cerebro-spinal system. There is a 
wide difference of opinion, however, concerning the immediate 
source and the histogenesis of these cells. 

Two views have been prevalent among the older investigators. 
Onodi advanced the idea that the cells at the distal ends of the 
spinal ganglia are forced to advance farther peripherally by the 
pressure exerted by the newly formed elements back of them. In 
this manner cell-groups become constricted off from the spinal 
ganglia and give rise to the anlagen of the sympathetic trunks. 
His, His, Jr., and some of the later writers have traced the origin 
of the cells giving rise to the sympathetic anlagen to the spinal 
ganglia, but have accounted for the transfer of these elements 
from the spinal ganglia to their new location by active migra- 
tion, either directly through the mesenchyme or along the paths 
of the spinal nerves and the communicating rami. 

The difference between these two views may be accounted for 
in part by fundamental differences in the morphogenesis of the 
sympathetic nervous system in the various classes of vertebrates. 



220 



ALBERT KUNTZ 



close proximity with each other that the entire anlage of the 
sjnnpathetic trunk appears as a continuous cell-column. This 
cell-column is not of uniform diameter, but in transverse sections 
traces of it are not wanting in any section in the thoracic and the 
dorsal region. Fibers are not present as yet either in the anlagen 
of the sympathetic trunks or in the communicating rami. The 
sympathetic anlagen are essentially cellular. The cells are 
closely aggregated and many of them present delicate protoplas- 
mic processes, or are included in small syncji;ia. These struc- 
tures are not very apparent in transverse sections, but in sagittal 
or frontal sections the anlagen of the sympathetic trunks present 
the appearance of a loose-meshed cellular network. 




mes. p/.a. 



-supr 



Fig, a. Diagrammatic transverse section of an embryo 12 mm. in length 
through the suprarenal bodies, X 50. 



SYMPATHETIC SYSTEM IN MAMMALS 



221 



'§ I 4 , f 




I F &^/^^ -p^^ ^ Section showing the path of the com- 

§/ nu municating ramus in an embryo 9 in mm. length, 

X 210. (See reference letters below.) 



REFERENCE LETTERS OF FIGURES 

{Except Fig. 16) 

All of the figures were drawn with the aid of the camera lucida or the projection 
lantern. A uniform scale of magnification was not adopted, but the scale of 
diameters of the drawing as reproduced is given in the description of each figure. 



a. 2. c. -Accompanying indifferent cells. 

ao. -Aorta. 

6. ?'ec. -Branch of recurrent nerve. 

ca.-Carotid artery. 

car. n.-Cardiac nerves. 

car. 6. -Anlagen of cardiac plexus. 

c.r. -Communicating ramus. 

c.?n.rf.n.r. -Cells migrating into dorsal 
nerve-root. 

c.??2.pv. -Cells migrating from sympa- 
thetic trunks into prevertebral plex- 
uses. 

c.m.y.r. -Cells migrating into ventral 
nerve-root. 

c.m.vagr.r. -Cells migrating into vagus 
rootlets. 

d.n.r. -Dorsal nerve-root. 

e.L?n. -External limiting membrane. 

/.py. -Fibers extending into preverte- 
bral plexuses. 

^.c.-Germinal cells of His. 

i.c.c.r.-Indifferent cells in communica- 
ting ramus. 



f.Lm. -Internal limiting membrane, 
wes. -Mesentery, 
w.r. /.-Motor root-fibers, 
m.s. p. -Anlage of myenteric and sub- 
mucous plexuses. 
n6. -Neuroblasts. 
oe.-CEsophagus. 

o.rec.n. -Origin of recurrent nerve, 
p. a. -Pulmonary artery. 
pv.a.-Anlagen of prevertebral plexuses, 
rec. n.-Recurrent nerve, 
sp.gr. -Spinal ganglion, 
sp.n. -Spinal nerve. 
s.r./.-Sensory root-fibers. 
swpr.-Suprarenal bodies. 
s?/,-Anlagen of sympathetic trunks. 
i.-Trachea. 
ya^r. -Vagus trunk, 
i^agr. 6. -Branch of vagus nerve. 
?;agr.r. -Rootlets of vagus nerve, 
y.n.r. -Ventral nerve-root. 



224 



ALBERT KUNTZ 




aia- 



FiG. 4. Transverse section of the neural tube and the anlage of the sym- 
pathetic trunk of an embryo 11 mm. in length, X 125. 



evidence of the migration of medullary cells from the neural tube 
is found in embryos about 4.5 mm. in length. At this stage the 
neural crest is not yet differentiated into ganglia, but appears as 
an inconspicuous ridge spreading laterally from the median dorsal 
line of the neural tube. It is so inconspicuous indeed that in 
many sections it may be distinguished only under favorable con- 
ditions. In a few instances the fibers of the ventral nerve-roots 
have penetrated the walls of the neural tube and are accompanied 



SYMPATHETIC SYSTEM IN MAMMALS 



225 



by medullary cells which have broken through the external limit- 
ing membrane. 

In embryos 7 mm. in length, the spinal ganglia are distinct, but 
are not completely formed as yet, and have receded but a short 
distance from the point at which the fibers of the dorsal nerve- 
roots enter the neural tube. In transverse sections, numerous 
breaches may be observed in the external limiting membrane in 










chivr. mrf "nib. 



Fig. 5. Transverse section of the ventral part of the neural tube of an em- 
bryo 9 mm. in length, showing cells migrating into the ventral nerve-root. X 250. 



the region of the dorsal nerve-roots. Rows of cells practically 
touching each other end to end may be traced from the mantle 
layer, through these breaches, into the proximal parts of the dor- 
sal nerve-roots (fig. 3, c.m.d.n.r.). Further evidence for the 
migration of medullary cells into the dorsal nerve-roots is pre- 
sented by the fact that in many sections where no breaches occur, 
cells are crowded close to the external limiting membrane in this 
region. In embryos 9 mm., and over in length, this area is always 



228 



ALBERT KUNTZ 



zontal line represent the lengths of the embryos in nun. ; the figures 
in the vertical line indicate the number of cells present in a given 
length of longitudinal sections of the spinal nerves, as they appear 
in transverse sections of the embryos, taken at random between 
the point of union of the sensory and the motor roots and the 
origin of the communicating rami. Embryos which seemed to 
be most normal in their development were selected, and the curve 
is based on the averages of ten independent counts. This curve 




Fig. 7. Diagrammatic transverse section of an embryo 9 or 10 mm. in length. 
The arrows indicate the course and the direction of the cells migrating from the 
neural tube and the spinal ganglia into the sympathetic anlagen. 
ao., Aorta, c.r., Path of communicating ramus, d.n.r., Dorsal nerve-root, pv.a., 
Anlagen of prevertebral plexuses, sp.g., Spinal ganglion, sp.n., Spinal nerve. 
supr., Suprarenal bodies, sy., Sympathetic trunks, v.n.r., Ventral nerve-root. 
w.h., Wolffian body. 



indicates that the rate of migration reaches its maximum in em- 
bryos 9 mm. in length, and that migration practically ceases 
when a length of 13 mm. is attained. It also indicates that a 
relatively small but fairly constant number of cells remains in 
the spinal nerves after migration has ceased. 

As already indicated in reviewing the literature, Kohn and Neu- 
mayer have attempted to account for the cells giving rise to the 
sympathetic nervous system, by local differentiation of elements 



SYMPATHETIC SYSTEM IN MAMMALS 



229 



already present in the sensory and the motor nerve-roots. This 
view seems to be quite generally accepted by the advocates of 
the theory of local differentiation and the multicellular nature 
of nerve-fibers. These two conceptions obviously go hand in 
hand. It is not the writer's purpose to discuss the nature of 
nerve-fibers. Suffice it to say that in the light of the recent inves- 
tigations of Cajal, Harrison, and others, the neurone theory 



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n 



Fig 8 . Curve designed to indicate the relative rate of migration of cells from 
the neural tube and the spinal ganglia along the spinal nerves, in successive stages 
of development. For explanation see text. 

seems to be firmly established. On the other hand, if the '^accom- 
panying" cells do not migrate peripherally we cannot account 
for the rapid decrease in the number of such cells present in the 
proximal part of the spinal nerves, which, as shown in fig. 8, 
takes place in embryos from 9 to 13 mm. in length. Mitotic 
figures occur occasionally in the nerve-roots as well as in the 
nerve-trunks and in the communicating rami. Doubtless, many 



THE JOURNAL, OF COMPARATIVE NEUROLOGY AND PSYCHOLOGY, VOL. 20, NO. 3. 



230 ALBERT KUNTZ 

of the ^' accompanying" cells arise by the mitotic division of ^in- 
different" cells along the course of migration, but these mitotic 
figures are by no means sufficiently numerous to account for the 
multitudes of cells which take part in the development of the 
sympathetic trunks. Furthermore, I have observed cells along 
the spinal nerves and the communicating rami, which, as will be 
shown later, are neuroblasts. Such cells were recently described 
by Cajal ('08) in the spinal nerves, and the communicating rami 
in embryos of the chick. According to Cajal, ^ Hhese neuroblasts 
do not correspond to the neurocytes of Kohn, but to the real motor 
cells in the neural tube." These facts are incompatible with 
the theory of local differentiation. 

(c) Later development. — In embryos 12 mm. in length, the an- 
lagen of the sympathetic trunks are rapidly becoming fibrous. 
They still appear as continuous cell-columns showing little evi- 
dence of their future segmental character. The earliest fibers 
of the longitudinal commissures, therefore, do not grow out through 
the inter-gangliar spaces, but the cells become aggregated into 
distinct ganglia after the sympathetic trunks have become fibrous. 
^^Accompanying" cells are still present along the spinal nerves 
and the communicating rami, but they are notably fewer than in 
the preceding stages. Cells may still be observed migrating 
from the neural tube and the spinal ganglia, but such migration 
probably does not continue far beyond this stage. In embryos 
over 12 mm. in length, the motor niduli are sharply limited, and 
medullary cells are rarely seen along the fibers of the ventral nerve- 
roots as they traverse the marginal veil. The spinal ganglia 
are also becoming more sharply limited distally, and cells no 
longer become separated from them. The later development of 
the sympathetic trunks consists in progressive changes and growth 
of the elements already present. 

(d) Nature of migrating cells. — In his excellent work on the 
earliest differentiations in the central nervous system, Schaper 
('97) made a most thorough and detailed study of the cells which 
arise by the mitotic division of the ^'germinal" cells (Keimzellen) 
of His. These cells were originally described by His as cells 



SYMPATHETIC SYSTEM iN MAMMALS 



231 





mc. 



Fig. 9 



Fig. 10 



Fig. 9 . Diagram illustrating the developmental relationships of the neuroblasts 
and the embryonic supporting cells in the neural tube of mammalian embryos 
(modified from Schaper, '97). Elongated dotted cells = ependymal cells; large 
circular cells with crosses = germinal cells of His; plain rounded cells = indifferent 
cells; rounded cells with dotted .crosses = indifferent cells which undergo 
further division by mitosis; rounded cells with dotsin center = neuroglia cells; 
block cells = nerve cells. 

Fig. 10. Ganglion cells, neuroblasts, and indifferent cells, X 1100. a., Cells in 
the spinal ganglia. 6., Neuroblasts in the ventral nerve-roots, c. Neuroblasts in 
the spinal nerve trunks, d., Bundles of fibers with accompanying indifferent 
cells, from the spinal nerves, e., Neuroblasts in the communicating ramus. /,, 
Neuroblasts in the anlagen of the sympathetic trunks. 



of ectodermal origin undergoing mitotic division near the inter- 
nal limiting membrane of the embryonic neural tube, giving rise 
to cells which develop into neuroblasts. Schaper has shown that 
the cells arising by the mitotic division of the ^'germinal" cells 
of His do not all develop into neuroblasts. They are cells of an 
indifferent character. In the lower vertebrates they are trans- 
formed either into neuroblasts or into embryonic supporting 
cells. In the higher vertebrates, however, many of these ^^in- 
different" cells retain a capacity for further propagation by di- 



232 ALBERT KUNTZ 

vision and give rise to new generations of ''indifferent" cells 
which may develop either into neuroblasts or into embryonic 
supporting cells. The accompanying figure (fig. 9), modified 
from Schaper, has been introduced to illustrate the developmental 
relationships of the neurones and the supporting elements in the 
embryonic nervous system. According to Schaper's original 
description, the ''indifferent" cells are characterized by large 
rounded nuclei showing a delicate chromatin structure, and very 
little cytoplasm. The "neuroblasts" are characterized by large 
rounded nuclei showing little structure in the interior except a 
well defined nucleolus, and a larger c}i:oplasmic body which is 
early drawn out to a point at one side. 

The great majority of the cells migrating from the neural tube 
and the spinal ganglia, along the spinal nerves and the conamuni- 
cating rami in embryos of the pig, answer to the description of 
the "indifferent" cells of Schaper. When observed in the motor 
niduli or in the distal ends of the spinal ganglia, their nuclei usu- 
ally appear more or less rounded in outline and show a very 
delicate chromatin structure. The c\i:oplasm is so meager that 
it can be observed only under the most favorable conditions. As 
these cells migrate peripherally the}" assume a more elongated 
form. In the ventral nerve-roots many of them have assumed 
their maximum elongation soon after they have left the neural 
tube. In the lines of cells which may be observed migrating 
out of the neural tube, the inner ones are often nearly circular 
in outline, the outer ones are greatly elongated, while those in in- 
termediate positions show varying degrees of elongation. This 
elongation cannot be accounted for mechanically, as by the 
squeezing through a narrow aperture in the external limiting 
membrane. These apertures are usually broad enough to per- 
mit free passage of the cells. It is probably due to more subtle 
forces which are operative in the process of migration. Further- 
more, it is by no means certain that such a change of shape al- 
ways takes place. Rounded "indifferent" cells are sometimes 
observed far distally along the course of migration, while elon- 
gated cells are present in the motor niduli and in the distal ends 
of the spinal ganglia. 



SYMPATHETIC SYSTEM TN MAMMALS 233 

Among the ^indifferent" cells of Schaper, cells are occasionally 
found which are characterized by large rounded or elongated 
nuclei showing a well defined nucleolus and very little chromatin 
structure, and a considerable quantity of cytoplasm which is 
usually drawn out to a point at one side (fig. 10). These cells 
are obviously the ^'neuroblasts" of Schaper. They are few in 
number, but occur all along the path of migration of the sympa- 
thetic cells. I have observed them in the ventral nerve-roots 
both inside and outside the external limiting membrane, in the 
spinal nerves, in the communicating rami, and in the anlagen of 
the sympathetic trunks. 

The histogenetic relationships of the cells taking part in the 
development of the sympathetic trunks will be considered further 
in section V. The facts of importance at this point are that 
cells which are endowed with a capacity to develop into neurones, 
migrate peripherally from the neural tube and the spinal ganglia, 
and that some of these cells migrate into the anlagen of the sym- 
pathetic trunks. These facts establish a direct genetic relation- 
ship between the sympathetic and the central nervous system. 
We are not to suppose, however, that all the cells taking part in 
the development of the sympathetic trunks actually migrate as 
such from their sources in the neural tube and the spinal ganglia. 
Doubtless, many arise by the mitotic division of 'indifferent" 
cells along the course of migration. The sources of these migrat- 
ing elements are, therefore, sufficient to account for all the cells 
which take part in the development of the sympathetic trunks 
and the sympathetic plexuses genetically related to them. 

II. PREVERTEBRAL PLEXUSES 

(a) Development. — In embryos 10 mm. in length, the anlagen 
of the prevertebral plexuses may be recognized as small cell- 
aggregates lying along the ventro-lateral surfaces of the aorta in 
the dorsal and the lumbar regions. In these regions the sympa- 
thetic trunks are not sharply limited ventrally. Cells become 
separated from their ventral margins and migrate ventrally along 
the sides of the aorta (fig. 11, c.m.pv.). In the region of the 



234 



ALBEHT Kr:VTZ 



suprarenals, such cells have descended as far as the mesial sur- 
faces of these bodies which, at this time, appear as compact ceU- 
colunms m^ore or less circular in transverse section, hing parallel 
with the aorta a short distance from its ventro-lateral surfaces 
(fig. 11, supr.). Posterior to the suprarenals, small cell-aggre- 
gates are present aU along the ventro-lateral surfaces of the aorta 
as far as the origin of the ihac arteries. It is impossible, in this 
stage, to determine the limits of the anlagen of the several sath- 



'^* '*>••• 



cmp 




Fig. 11. Transverse section through the sympathetic trunks and the supra- 
renal bodies of an embryo 9 mm. in length, X 150. 



pathetic plexuses in this region. The only distinction between 
the ceU-aggregates which constitute the anlagen of the coehac. 
the renal, the abdominal aortic, and the hj-pogastric plexuses 
consists in a difference in degree of development . Development 
proceeds somewhat more rapidly in the anterior than in the pos- 
terior region. In transverse sections thi'ough this region, traces 
of one or the other of these plexuses appear in nearly every sec- 
tion. 



SYMPATHETIC SYSTEM IN MAMMALS 235 

In embryos 13 mm. in length, the cell-aggregates lying along 
the ventro-lateral surfaces of the aorta have become more pro- 
nounced. The greatest development occurs in the region of the 
suprarenals. At a few points, fibers may be traced from the 
sympathetic trunks into the anlagen of the prevertebral plexuses 
(fig. 12, f.pv.). In the region of the cceliac plexus, fibers have 
advanced farther peripherally and may be traced for a short 
distance into the mesentery. The anlagen of the abdominal 
aortic plexus have developed into a loose network which com- 
pletely surrounds the aorta ventrally. 

In embryos 16 mm. in length, the prevertebral plexuses are 
becoming more distinct and more fibrous. The sympathetic 
trunks are more sharply limited ventrally, except in the region 
of the suprarenals. At this point there is still a continuous line 
of sympathetic cells extending from the sympathetic trunks into 
the cell-aggregates associated with the suprarenals. 

(6) Histogenetic relationships. — The cells constituting the an- 
lagen of the prevertebral plexuses show all the characters of the 
cells present in the sympathetic trunks. Continuous lines of 
cells may be traced from the latter into the former. The prever- 
tebral plexuses, therefore, stand in direct genetic relationship 
to the sympathetic trunks. Mitotic figures occur occasionally 
along the courses of migration from the sympathetic trunks as 
well as in the anlagen of the prevertebral plexuses. Doubtless, 
a goodly number of the cells taking part in the development of 
the prevertebral plexuses arise by the mitotic division of '^in- 
different" cells along the courses of migration. The develop- 
ment of the prevertebral plexuses is, therefore, entirely analogous 
with the development of the sympathetic trunks. 

III. VAGAL SYMPATHETIC PLEXUSES 

(a) Introductory. — Under the term vagal sympathetic plex- 
uses, we shall consider those plexuses, usually regarded as sym- 
pathetic, which are directly related to the vagi; viz., the cardiac 
plexus and the sympathetic plexuses in the walls of the «. visceral 
organs. 



236 



ALBERT KUNTZ 







anpv^t.1% 



Fig. 12. Transverse section through the sympathetic trunks and the anlagen 
of the coeliac plexus of an embryo 12 nun. in length, X 150. 

Our knowledge concerning the development of the sympathetic 
plexuses related to the vagi is very limited. The older workers 
generally gave little attention to the peripheral sympathetic 
plexuses. Onodi ('86), though he traced the origin of the sym- 
pathetic trunks and the prevertebral plexuses to the spinal gan- 
glia, could not derive the peripheral sympathetic plexuses from the 
same source, because he found no cellular connections between 
the latter and the sympathetic trunks. He believed it necessary, 
therefore, to cling to the doctrine of Remak ('47) with regard to 
the peripheral sympathetic plexuses and derive them from the 
mesoderm. His, Jr., ('91) traced the origin of the peripheral 
sympathetic plexuses, including the sympathetic plexuses in the 
walls of the digestive tube and the sympathetic components re- 
lated to the vagi, to cell-swarms which migrate peripherally from 
the anlagen of the sympathetic trunks. 



SYMPATHETIC SYSTFM IN MAMMALS 237 

Later writers have generally assumed that the cardiac plexus 
and the sympathetic plexuses in the walls of the visceral organs 
have their origin in the sympathetic trunks, but the course of their 
development has not been made clear. The literature bearing 
on this point is conspicuously meager. 

My own observations, as indicated in a recent paper, ^ have 
shown that the cardiac plexus and the sympathetic plexuses in 
the walls of the visceral organs do not owe their origin to the sym- 
pathetic trunks as has hitherto been supposed, but that they arise 
from cells which migrate from the vagus ganglia and the walls of 
the hind-brain along the fibers of the vagi. 

Because the origin of these plexuses is distinct and separate from 
the origin of the sympathetic trunks and the sympathetic plex- 
uses described above as prevertebral plexuses, they cannot prop- 
erly be characterized as prevertebral sympathetic plexuses. 
In view of their relation to the vagi I have chosen to designate 
them as vagal sympathetic plexuses. The term "vagal sympa- 
thetic" is a departure from the established nomenclature, but 
inasmuch as there is no good collective term which could be ap- 
plied to the cardiac plexus and the sympathetic plexuses in the 
walls of the visceral organs, it has seemed well, for the sake of 
clearness, to employ a new term. 

(6) Myenteric and submucous plexuses. — In transverse sections 
of embryos 6 and 7 mm. in length, in the region of the oesophagus, 
the vagus trunks appear as large bundles of loosely aggregated 
fibers accompanied by numerous rounded or elongated cells. 
These cells, which, as will be shown later, are of medullary and 
ganglionic origin, are easily distinguished from the cells of the 
surrounding mesenchyme by their larger size and the character- 
istic chromatin structure of their nuclei. Many of them appear 
to become separated from the nerve-trunks and to wander into 
the walls of the oesophagus until the latter is completely surrounded 
by these migrant cells. In a few sections short fibers are seen to 
bend from the vagus trunks toward the oesophagus (fig. 13, vag. 



2 The role of the vagi in the development of the sympathetic nervous system. 
Anatomischer Anzeiger, Bd. 35, no. 15, 16, pp. 381-390. 



238 ALBEET KUNTZ 

b.)- From the tips of these growing fibers, cells pass in well 
defined paths into the walls of the oesophagus. It is probable 
that most of the cells which become separated from the vagi 
wander out along the fibers of these growing branches. The cells 
which have wandered into the walls of the oesophagus are not 
arranged in well defined rings as yet, bu^" are loosely scattered in 
the tissues (fig. 13, m.s.p.). 

The fibers of the vagi do not yet extend beyond the region of the 
heart. In transverse sections through the stomach, the paths of 
the vagus branches are indicated by the presence of numerous 



nisp. 



""^SKo e" ^ 




Fig. 13. Transverse section through the oesophagus and the vagus trunks in 
an embryo 7 mm. in length, X 160. 



cells like those described above. These cells show a tendency to 
spread until they have completely surrounded the walls of the 
stomach. Similar cells are found scattered in the walls of 
the intestine as far as the latter can be traced. Thus, it appears 
that, having once become established in the anterior region of the 
digestive tube, these cells migrate posteriorly along its course. 

That these migrant nervous elements found in the walls of the 
digestive tube have migrated thither from the vagus trunks can- 
not be doubted. There is no difficulty in tracing cells from the 



SYMPATHETIC SYSTEM IN MAMMALS 239 

tipsof the growing branches of the vagi into the walls of the oesopha- 
gus. Furthermore, it is impossible to trace cells from any other 
source. There is no evidence as yet of the migration of cells 
from, the sympathetic trunks or from the prevertebral plexuses 
toward the walls of the digestive tube. Neither cellular nor 
fibrouS connections occur between the sympathetic trunks or the 
prevertebral plexuses and the sympathetic plexuses in the walls 
of the digestive tube until the latter have become well established. 

In transverse sections of embryos 9 mm. in length, there is no 
evidence of cells wandering from the vagus trunks toward the 
oesophagus except along the fibers of the growing branches. These 
courses are still plainly visible. The migrant cells in the walls of 
the oesophagus have become arranged in more definite rings, and 
none are found scattered in the surrounding tissue. Numerous 
cells still accompany the fibers of the vagi all along their course 
and seem to escape freely at their growing tips. 

In embryos 12 mm. in length, the number of cells in the prox- 
iriial part of the vagus trunks has materially decreased. Most of 
those still remaining probably subserve a supporting function. 
The more distal parts still contain numerous cells. It is probable, 
however, that the migration of cells along the vagi does not con- 
tinue far beyond this stage. In the region just anterior to the 
stomach, the vagus trunks have broken up into a loose network 
which is the beginning of the oesophageal plexus. Vagus fibers 
still accompanied by numerous cells may now be traced along the 
lesser curvature of the stomach. The anlagen of the coeliac 
plexus are well established, but there are no fibrous connections 
as yet between them and the anlagen of the sympathetic plexuses 
in the walls of the digestive tube. 

In embryos 16 mm. in length, the vagus trunks as well as their 
branches, many of which have established connections with the 
myenteric and the submucous plexuses, are apparently free from 
migrating cells. In the walls of the oesophagus, the cells which 
have wandered in are aggregated into more or less distinct groups 
arranged in two broken rings. The myenteric and the submu- 
cous plexuses are thus becoming distinct. A similar arrangement, 
though less definite, is apparent also in the walls of the intestine. 



240 ALBERT KIJNTZ 

Fibrous connections have become established "^ith the sympa- 
thetic trimks as well as with the coehac and the h^-pogastric 
plexuses. It is interesting to note that all these s}Tapathetic 
ner\'es still contain niii:-^r:us ■"accompan^dng" cells which are 
apparently migrating peripherally along their fibers. It is prob- 
able, therefore, that cells wander do^Ti from the s^Tnpathetic 
tninks into the myenteric and the submucous plexuses after these 
fibrous connections are estabhshed. 

(c Pulmonary plexuses. — In transverse sections of embryos 
6 or 7 ram. in length, some of the cells which wander from the 
vagus trunks toward the oesophagus, in the region of the bifurca- 
tion of the trachea, are carried out along the anterior and the dor- 
sal surfaces of the bronchi. These cells ob^dously give rise to the 
anlagen of the pulmonary plexuses. 

(d) Cardiac plexus. — The fii'st immistakable evidence of gan- 
glia pertaining to the cardiac plexus is found in embryos about 12 
mm. in length. In transverse sections thi'ough the anterior 
region of the heart, small ^T^aips of ner^'ous elements are observed 
ventral to the trachea ng. 14. car. p.), a few of which have pene- 
trated deep into the angle between the aorta and the pulmonary 
artery. These ceU-aggregates constitute the anlagen of the earh- 
est gangha of the carchac plexus. They are without fibrous con- 
nections as yet. but a few short fibrous branches are seen to arise 
from the vagus trunks and the left recurrent ner\^e, which extend 
toward the heart (fig. 14, cam . These are obviously the earhest 
cardiac nerves. Their fibers ar- -tiU loosely aggregated and are 
accompanied by nimierous cell.-, some of which appear to escape 
at the tips of the nerves and to migrate toward the cardiac gan- 
gha in advance of the growing fibers. Xerves cannot be traced 
as yet from the s^Tnpathetic tnmks toward the heart, and there 
is no evidence of the migration of cells from the s^Tnpathetic 
trunks into the anlagen of the cardiac plexus. 

In embryos 16 nun. in length, branches of the vagi as weU as 
cardiac nerves ha^-ing their origin in the s^Tupathetic trunks may 
be traced into the gangha of the carchac plexus. Here again it is 
interesting to note that while the branches of the vagi are appar- 
entlv free from misrrating ceUs. the carchac ner^'es haA-ing their 



SYMPATHETIC SYSTEM IN MAMMALS 



241 




A A 







f^ .5 



^ ^" ^ ^^ ^'1 ao 




,-brec. 



vog. 
orc'cn 







Fig. 14. Transverse section through the oesophagus, the vagus trunks, and 
the anlagen of the cardiac plexus in an embryo 13 mm. in length, X 100. 



origin in the sympathetic trunks still contain numerous '^accom- 
panying" cells which are apparently migrating peripherally along 
their fibers. It is probable, therefore, that the cardiac plexus 
also receives cells from the sympathetic trunks after the sympa- 
thetic cardiac nerves have become established. 

This stage in the pig may be compared with the human embryo 
10.2 mm. in length described by His, Jr. ('91). He also observed 
that, in this stage, the branches of the vagi are comparatively 
free from cells, while the cardiac nerves having their origin in the 
sympathetic trunks contain many cellular elements. He con- 



242 ALBERr KUNTZ 

eluded, therefore, that the gangha of the cardiac plexus are com- 
posed exclusively of cells which have migrated thither from the 
sjTiipathetic trunks. 

The above observations prove conclusively that the earliest 
anlagen of the cardiac plexus in the pig arise from cells which 
migrate thither from the vagus trunks. This is probably true 
for all mammals. In the human embryo of His, Jr., referred to 
above, the cardiac plexus already had fibrous connections with 
both the vagi and the s^Tiipathetic trunks. The anlagen of the 
cardiac plexus would probably have been found considerably 
earher. 

My observations on the later development of the cardiac plexus 
in the pig do not differ essentially from those of His, Jr. ,2 on the 
human embryo, except that the earliest cardiac nerves having 
their origm in the sympathetic trunks are less intimately asso- 
ciated with the vagi, and enter the cardiac plexus independently. 
This fact was also observed by His, Jr., in embryos of the cat. 

(e) Cell migration along the vagi.^In sections taken at right 
angles to the axis of the trunk, in the head region of embryos 9 
or 10 mm. in length, medullary cells may be observed migrating 
from the walls of the hind-brain into the rootlets of the vagus and 
the spinal accessory nerves (fig. 15, c.m.vag.r.). That these 
cells wander out in considerable numbers cannot be doubted. 
In many sections medullary cells are observed drawn out into cone- 
shaped heaps in the nerve-rootlets as they traverse the marginal 
veil. Occasionally one of these cells is observed half in and half 
out of the neural tube, and many are present in the nerve-rootlets 
just outside the external limitmg membrane. 

In sagittal sections the entire vagus trunk is seen to contain 
many of these ^'accompanA^ing" cells which are apparently mi- 
grating peripherally. The ganghon of the trunk is, at this stage, 
a somewhat irregular oval or elliptical body which is not sharply 
limited distally. Cells appear to become separated from its dis- 
tal end and to wander peripherall}^ along the vagus trunk. Mi- 



3 Ahhdl. Math-physischen Classe d. Konigl. Sachs. Gesell. d. Wiss. Bd. 8, Leipzig 
1891. 



SYMPATHETIC SYSTEM IN MAMMALS 



243 



totic figures occur frequently in the ganglion of the trunk and 
occasionally all along the vagus nerve. 

The course and the direction of the cells migrating peripherally 
along the fibers of the vagi are indicated by the arrows in fig. 16. 
That these cells actually migrate peripherally cannot be doubted. 
The number of ^'accompanying" cells present in the vagus trunks 
increases rapidly until a maximum number is reached in embryos 
9 or 10 mm. in length; then it decreases rapidly until the embryos 







Fig. 15. Section through the rootlets of the vagus nerve in an embryo 10 
mm. in length, taken at right angles to the axis of the trunk, X 270. 



have attained a length of about 13 mm., when only a relatively 
small number of cells remains distributed along the nerve-fibers. 
These phenomena can be explained on no other ground. Again, 
the preparations studied show figures of cells escaping from the 
growing branches of the vagi into the anlagenof the cardiac plexus 
and the sympathetic plexuses in the walls of the visceral organs 
which are perfectly clear, and can be interpreted only to mean 
that these are the cells which give rise to the vagal sympathetic 
plexuses. 

The majority of the cells migrating peripherally along the fibers 
of the vagi are characterized by large rounded or elongated nuclei 
showing a delicate chromatin structure, and very little cytoplasm. 



244 



ALBERT KUNTZ 



These are ob^'iously the ^'indifferent" cells of Schaper. Among 
these, other cells occasionally are found which are characterized 
b^^ large rounded or elongated nuclei showing a well defined nucle- 
olus and very little chromatin structure, and a larger CAiioplasmic 
body which is usually drawn out to a point at one side (fig. 17). 
These cells are obviously the ^^neuroblasts" of Schaper. From 
this description it is ob^dous that the cells which migrate from 




Fig 16 . Diagram designed to show the relation of the vagi to the vagal sympa- 
thetic plexuses. The arrows indicate the course and the direction of the ceEs mi- 
grating from the walls of the hind-brain and the vagus ganglia into the anlagen 
of the vagal sjinpathetic plexuses. 

a. a.. Aortic arch, aw., Auricle. 6. c. Buccal cavity. 6r., Bronchi, car. p., Anlagen 
of cardiac plexus. c6.L. Cerebellum. /. 5., Fore-brain, g.f.. Ganglion of the trunk, 
m. 6., Mid-brain. m.o6.. Medulla oblongata. ?i.f., Neural tube, oe., CEsophagus. 
oe.p., (Esophageal plexus, p. a.. Pulmonary artery, -sf.. Stomach. /., Trachea. 
ten.. Ventricle, ven, IV., Fourth ventricle, p.t., Vagus trunk. 10., Roots of vagus 
nerve. 11., Roots of spinal accessory ner^^e. 12., Roots of hjT>oglossal nerve. 
c./.. First cer^dcal nerve. 



the vagus gangha and the walls of the hiad-braia along the vagi 
are cells of the same character as those which migrate from the 
neural tube and the spinal ganglia along the spinal ner^^es. 

The above observations prove conclusively that the myenteric 
and the submucous plexuses^ the pulmonar}' iDlexuses, and the 



SYMPATHETIC SYSTEM IN MAMMALS 245 

cardiac plexus have a common origin which is distinct and sepa- 
rate from the origin of the sympathetic trunks. They arise from 
cells which have their origin in the vagus ganglia and the walls 
of the hind-brain. As in the case of the sympathetic trunks, 
however, we are not to suppose that all the cells taking part 
in the development of the vagal sympathetic plexuses actually 
migrate as such from their sources in the cerebro-spinal nervous 
system. Doubtless, many arise by the mitotic division of ^in- 
different" cells along the course of migration and in the anlagen 
of these plexuses. The vagus ganglia and the walls of the hind- 
brain, therefore, constitute a source which is sufficient to account 



a. 








Fig. 17. Neuroblasts and indifferent cells located in the vagi and the ganglia 
of the trunk, X 1100. 

a.. Neuroblast in the vagus rootlets, b., Neuroblasts in the vagus trunks, c, 
Neuroblasts in the ganglia of the trunk, d., Bundles of fibers with accompanying 
indifferent cells, from the vagus trunks. 

for all the cells which take part in the early development of the 
vagal sympathetic plexuses. Migrant cells cannot be traced from 
the sympathetic trunks into the anlagen of these plexuses until 
the nerves connecting the latter with the sympathetic trunks are 
present. At this time the vagal sympathetic plexuses are well 
established, and the great majority of the cells taking part in 
their development are already present. We may conclude, there- 
fore, that the nerves entering the vagal sympathetic plexuses 



246 ALBERT KUNTZ 

from the sympathetic trmiks represent later connections, and 
play onh^ a secondary part in their development. 

These conclusions differ widely from the views hitherto gener- 
ally accepted concerning the development of the cardiac plexus 
and the sjonpathetic plexuses in the walls of the visceral organs, 
but the facts on which they are based are perfectly clear. Fur- 
thermore, the}' obviate certam difficulties which arise m any 
attempt to derive these plexuses from the s^Tiipathetic trunks. 
The anlagen of the sympathetic plexuses in the walls of the vis- 
ceral organs are present before any traces of the prevertebral 
plexuses or of cells migrating peripherally from the s^^npathetic 
trunks are found. It is obvious, therefore, that the vagal sym- 
pathetic plexuses cannot be derived from the SAHipathetic trunks. 
These findings also give the vagi an importance in the develop- 
ment of the sjTnpathetic nervous system which has hitherto been 
unrecognized, but which is m complete harmon}" \\dth other known 
facts. 

V. DISCUSSION OF RESULTS, AND CONCLUSIONS 

(a) Migration of medullary cells. — Neurological hterature con- 
tains frequent allusions to the migration of medullary cells ever 
since the time of Balfour ('75). That pioneer among the inves- 
tigators of the histogenesis of nerve-forming elements observed 
cells which he beheved to be nervous elements, migrating from 
the embryonic neural tube in elasmobranchs. These observa- 
tions were substantiated by Beard ('88) and Dohrn ('88, '91). 
Herrick ('93) observed medullary elements migratmg from the 
motor niduh mto the ventral roots of the spmal nerves in amphib- 
ians, reptiles, and mammals. Ganglion cells have also been found 
occasionally m the motor nerve-roots m adult animals. Such 
cells were observed by Freud ('78) in the ventral roots of the spinal 
nerves m Petromyzon, and by Schafer ('81) and KoUiker ('94) 
in the ventral roots of the spinal nerves m the cat. Thompson 
('87) described cells which he interpreted as degenerating gan- 
ghon cells, m the third and fourth cranial nerves in man. 

More recent investigators have frequently observed migrant 



SYMPATHETIC SYSTEM IN MAMMALS 247 

medullary cells and have variously interpreted them. Harrison 
('01) has shown that in the salmon the spinal ganglia arise from 
cells which migrate out from the dorsal region of the neural tube. 
He also observed medullary cells migrating into the ventral 
roots of the spinal nerves, and suggested the possibility that tnese 
cells may migrate peripherally into the gangha of the sympathetic 
trunks and there give rise to sympathetic excitatory neurones. 
Bardeen ('03) observed that in mammalian embryos a certain 
number of cells migrate from the neural tube and the spinal gan- 
glia along the fibers of the spinal nerves. He suggested that these 
cells take part in the development of the neurilemma. He be- 
lieves, however, with Vignal ('83) and Gurwitsch ('00), that in 
mammals the neurilemma is derived largely from the mesoderm. 
Neal ('03) described medullary cells in the ventral roots of the 
spinal nerves in Squalus acanthias, and expressed the opinion 
that they take part in the development of the neurilemma. Car- 
penter ('06) has shown that in embryos of the chick medullary 
cells which he recognizes as the 'indifferent" cells of Schaper, 
migrate from the walls of the mid-brain along the fibers of the 
abducent and the oculomotor nerves. According to Carpenter 
most of these cells become distributed along the nerve-trunks 
and may be recognized as the cells which give rise to the neuri- 
lemma. In the oculomotor nerve, however, some of these 'in- 
different" cells migrate farther peripherally and give rise to 
neurones in the ciliary ganglion. Carpenter and Main ('07) are 
of the opinion that some of the medullary cells which they ob- 
served migrating into the ventral roots of the spinal nerves in 
embryos of the pig become cells of the neurilemma and there sub- 
serve a supporting function similar to that of the neuroglia cells 
in the central nervous system. Cajal ('08) described elements 
which he recognizes as nerve cells in the bipolar phase, in the ven- 
tral roots of the spinal nerves and certain of the cranial nerves in 
the chick. 

Although the advocates of the theory of local differentiation 
and the multicellular nature of nerve-fibers reject the theory of 
the migration of nervous elements, the results of recent researches 
are so convincing that we must accept the migration of medullary 

THE JOURNAL OP COMPARATIVB NEUEOLOGY AND PSYCHOLOGY, VOL. 20, NO. 3. 



248 ALBERT. KUNTZ 

cells as a fact. The present series of observations shows, moreover 
that the migration of medullary elements plays a far more im- 
portant role in the development of the peripheral nervous system 
than has hitherto been admitted. Direct observations have 
shown that medullary cells migrate into the ventral roots of the 
spinal nerves and into the roots of several of the cranial nerves. 
The present observations have further shown that such cells 
migrate also into the dorsal roots of the spinal nerves and into 
the roots of the vagus and the spinal accessory nerves. I have 
also observed medullary cells migrating into the semilunar gan- 
glia. Furthermore, it has been shown that some of the cells 
which migrate peripherally from the neural tube and the cerebro- 
spinal ganglia give rise to the sympathetic nervous system. 

(h) The neurilemma: — An extended discussion of the develop- 
ment of the neurilemma is beyond the scope of this paper. Inas- 
much, however, as the histogenesis of the neurilemma is so inti- 
mately related to the histogenesis of the sympathetic neurones, 
its origin may be considered briefly at this point. As the '4ndiff- 
ent " cells migrate peripherally from the neural tube and the spinal 
ganglia, they migrate not only into the anlagen of the sympa- 
thetic trunks but also along the growing fibers beyond the origin of 
the communicating rami. These cells as well as the cells which, as 
has been shown, remain distributed along the nerve-trunks after 
migration has ceased, obviously take part in the development of 
the neurilemma, .^hey cannot be accounted for in any other way. 

Not a few of the more recent investigators, including the advo- 
cates of the theory of local differentiation and the multicellular 
nature of nerve-fibers, are of the opinion that the neurilemma is of 
ectodermal origin. We agree with the advocates of local differenti- 
ation on this point, but we must disagree with them as to the man- 
ner in which the cells giving rise to the neurilemma arise and are 
distributed along the nerve-fibers. It is significant that Kolliker 
('05), though formerly of the opinion that the neurilemma is of 
mesodermal origin, came to the conclusion, in his last research, 
that some of the cells which wander out from the spinal ganglia 
give rise to the neurilemma of the sensory fibers, and that the neuri- 
lemma is ever3rwhere of ectodermal origin. Carpenter ('06) has 



SYMPATHETIC SYSTEM IN MAMMALS 249 

shown that migrant medullary cells actually develop into cells 
of the neurilemma in the abducent and the oculomotor nerves in 
the chick. 

Proof of the medullary and the ganglionic origin of the cells 
giving rise to the neurilemma was difficult only until it could be 
demonstrated that cells actually migrate peripherally from the 
neural tube and the cerebro-spinal ganglia along both the spinal 
and the cranial nerves. The present series of observations pre- 
sents conclusive evidence on this point. We may here repeat 
what has already been stated with regard to the cells taking part 
in the development of the sympathetic system. We are not to 
suppose that all the cells taking part in the development of the 
neurilemma actually migrate as such from the neural tube and 
the cerebro-spinal ganglia. Doubtless, many arise by the mitotic 
division of ^^indifferent" cells along the course of migration. Ac- 
cording to this interpretation, the cells of the neurilemma are 
homologous with the neuroglia cells in the central nervous sys- 
tem. 

(c) Sympathetic excitatory and sympathetic sensory neurones. — 
The problem of the histogenetic relationships of the sympathetic 
excitatory and the sympathetic sensory neurones presents peculiar 
difficulties. The presence of sympathetic sensory neurones in the 
sympathetic trunks and prevertebral plexuses has not been demon- 
strated. Froriep, like Langley, Kolliker, and P. Schultz, denies the 
existence of sympathetic sensory neurones entirely. There can 
be little doubt, however, that sympathetic sensory neurones are 
present in the sympathetic plexuses in the walls of the digestive 
tube. According to Bayliss and Starling ('99), the peristaltic 
contractions of the small intestine are true coordinated reflexes 
carried out by the local nervous mechanism (myenteric plexus) . 
The later experimental work of Cannon ('06) and of Auer ('10) 
lends support to this view by showing that the peristaltic contrac- 
tions of the stomach and the intestine may be carried on more or 
less regularly for a considerable length of time after both the vagi 
and the splanchnic nerves have been severed. These phenomena 
seem to indicate the existence of true sensory neurones in the 
sympathetic plexuses in the walls of the digestive tube. 



250 ALBERT KrXlZ 

Froriep"s conclusion that the ?}inpathetic neurone? have their 
origin in the ventral hah of the nemal tube and migrate out along 
the fibers of the ventral roots of the spmal nerves is probably cor- 
rect with regard to the neurones in the SAinpathetic trimks and 
the prevertebral plexuses. I have sho^ii. however, that the vagal 
s^Tiipathetic plexuses arise from cells which migrate peripherally 
along the fibers of the vagi. If, as experimental evidence indi- 
cates, so ne of these plexuses contain sensor}- neurones, it is proba- 
ble that these arise from ceUs which migrate from the vagus gangha. 
TMiile it is impossible by dii^ect observation to trace either satq- 
pathetic excitatory or s^Tupathetic sensory elements back to theii' 
specific somTe in the cerebro-spinal nervous system, the facts at 
our command warrant the conclusion that the s\Tnpathetic excita- 
tory neurones arise from ceUs which migrate from the neiual tube 
along the fibers of the motor nerve roots, while the sympathetic 
sensory neurones, wherever such nem-ones exist, arise from cells 
which migrate from the cerebro-spinal gangha. 

The nervous elements in the neural crest obviously have the 
same origin as those which remain within the neural tube; they 
are the descendents of the "' germinal"" cells of His. Retzius has 
shown that m amphioxus sensory neurones are foimd hung near 
the mternal limiting membrane lining the sHt-like central canal, 
some of which send then dendidtes out to the skin. In the fishes 
also a relatively large number of cells remaining within the neural 
tube give rise to sensory fibers which rim to the skin. In embryos 
of the salmon, according to Harrison, ceUs become separated from 
the neural tube and. migrathig ventrally, give rise to the spinal 
ganglia. In embryos of the pig. as akeady indicated, medullary- 
cells migrate from the dorsal region of the neural tube into the dor- 
sal nerve-roots. All these facts suggest that the cerebro-spmal 
gangha have arisen from cells which originaUy lay withm the neu- 
ral tube, and mdicate the common origin of all sensory and motor 
neurones. 

The orientation of the ceUs in the neural tube, during the period 
of migration, is such that the cells which wander into the dorsal 
ner^-e-roots seem to have their origin hi the dorsal part of the 
neural tube, while those which migrate into the ventral nerve- 



SYMPATHETIC SYSTEM IN MAMMALS 251 

roots wander out frotn the ventral zone and from the region in 
which later the lateral horn of the gray matter arises. This also 
is in full accord with the conditions in the adult nervous system. 
The neurones in the cerebro-spinal ganglia, as far as is known, 
are sensory in character, while the cells whose axones constitute 
the fibers of the motor nerve-roots are located in the ventral part 
of the neural tube. Furthermore, the investigations of Kohn- 
stamm ('00) render the existence of efferent fibers in the dorsal 
nerve-roots of the higher vertebrates extremely doubtful. Inas- 
much as nervous elements which have the capacity to develop 
into neurones migrate peripherally along both the sensory and 
the motor nerve-roots, we are driven to the conclusion that the 
sympathetic excitatory elements migrate from the neural tube 
along the fibers of the motor nerve roots, while the sympathetic 
sensory neurones, wherever such neurones exist, arise from cells 
which wander out from the cerebro-spinal ganglia. This inter- 
pretation makes the sympathetic neurones entirely homologous 
with the efferent and the afferent components of the other func- 
tional divisions of the peripheral nervous system. 

(d) A wider application of Schaper^s conception. — As has been 
shown in the preceding pages, the cells which migrate peripherally 
from the neural tube and the cerebro-spinal ganglia have a com- 
mon origin; they are the descendants of the '' germinal'' cells of 
His ; viz . , the ' ' indifferent ' ' cells and the ' ' neuroblasts ' ' of Schaper . 
Therefore, Schaper's conception of the developmental relation- 
ships of the neurones and the supporting elements in the central 
nervous system may be extended to the sympathetic neurones 
and the cells of the neurilemma. 

(e) The relation of the sympathetic to the central nervous system. — 
In the light of the present investigation, the sympathetic system 
bears a direct genetic relationship to the central nervous system. 
The cells giving rise to the sympathetic trunks, and the preverte- 
bral plexuses migrate peripherally along the spinal nerves, while 
those giving rise to the vagal sympathetic plexuses migrate 
peripherally along the vagi. The cells giving rise to the sympa- 
thetic neurones, however, all have the same genetic relation- 
ships; they are the descendants of the '^germinal" cells of His. 



252 ALBEiir KUNTZ 

Therefore, the sympathetic neurones are homologous with the 
neurones in the central nervous system. 

The sympathetic system is not a nervous mechanism separate 
from the central nervous system, but the nervous system is a 
unit of which the sympathetic system is a part homologous with 
the other functional divisions. It may be looked upon as an acces- 
sion to the nervous system which has arisen comparatively late 
in the evolution of vertebrates, in response to an increasing demand 
for a nervous mechanism of a lower order, which might assume 
the direct control of the purely vegetative functions. 

(/) Functional relations. — The reader will, undoubtedly ask 
what bearing the facts set forth in the preceding pages may 
have on physiological and psychological problems involving the 
sympathetic system. This question we cannot hope to answer 
at present. We may, however, offer a few suggestions which 
have presented themselves during the progress of this investiga- 
tion. 

Our knowledge concerning the functional relations and the 
physiological activities of the sjnupathetic system is very limited. 
Nor could we hope for much progress in this direction as long as 
the developmental relationships of the sympathetic to the cen- 
tral nervous system were not definitely known. The fact that 
the sympathetic system is homologous with the other functional 
divisions of the nervous system lends a new aspect to the entire 
problem. The fact, however, that the vagal sympathetic plex- 
uses have their origin in the hind-brain and the vagus ganglia will 
probably be of even greater physiological and psychological im- 
portance. This fact indicates a close relationship between the 
lower centers of the brain and the innervation of the heart and 
the visceral org,ans. The suggestion is here ventured that in 
this relationship will probably be found the basis of certain phy- 
siological and psychological problems involving the digestive 
functions and the action of the heart, which have hitherto been 
obscure. 

Here is a field for investigation which challenges the attention of 
both the student of physiology and the student of psychology. 
It is beset with the greatest difficulties, but promises to be fruit- 
ful of the most far-reaching results. 



SYMPATHETIC SYSTEM IN MAMMALS 253 

VI. SUMMARY 

1. The sympathetic trunks arise as a pair of cell-columns 
lying along the sides of the dorsal surface of the aorta. In the 
early stages, medullary cells migrate from the neural tube into 
the dorsal and the ventral nerve-roots. The cells which migrate 
into the ventral nerve-roots, with similar cells which wander 
down from the spinal ganglia, mig;rate peripherally along the spi- 
nal nerves. Some of these cells deviate from the course of the 
spinal nerves and, migrating along the paths of the communicating 
rami, give rise to the sympathetic trunks. These findings differ 
materially from those of the earlier investigators. They agree 
essentially with the findings of Froriep. 

2. The prevertebral plexuses arise as cell-aggregates lying 
along the ventro-lateral aspects of the aorta in the posterior re- 
gion of the body. They are derived directly from the sympathetic 
trunks. 

3. The cardiac plexus and the sympathetic plexuses in the 
walls of the visceral organs are not derived from the sympathetic 
trunks, as has hitherto been supposed, but have their origin in 
nervous elements which migrate from the hind-brain and the vagus 
ganglia along the fibers of the vagi. In view of the relation of 
these plexuses to the vagi, the author has chosen to designate 
them as ^' vagal sympathetic" plexuses. These findings give the 
vagi an importance in the development of the sympathetic sys- 
tem which has hitherto been unrecognized. 

4. The cells migrating peripherally from the cerebro-spinal 
system along the spinal nerves and the vagi are the descen- 
dants of the ^^ germinal" cells of His; viz., the ^indifferent" 
cells and the ^^neuroblasts" of Schaper. Therefore they are 
homologous with the cells giving rise to the neurones and the 
supporting elements in the central nervous system. 

5. The cells migrating peripherally along the spinal nerves 
and the vagi do not all take part in the development of the sym- 
pathetic system. Some become distributed along the nerve- 
fibers and give rise to the neurilemma. Therefore, the cells of 



254 ALBERT KUNPZ 

the neurilemma are homologous with the neuroglia cells in the 
central nervous system. 

6. The cells taking part in the development of the sympa- 
thetic nervous system and the neurilemma do not all actually 
migrate as such from their sources in the cerebro-spinal system. 
Doubtless, many arise by the mitotic division of ^indifferent" 
cells along the course of migration. 

7. The existence of sympathetic sensory neurones in the sym- 
pathetic trunks and the prevertebral plexuses has not been demon- 
strated. Experimental evidence, however, indicates the presence 
of sympathetic sensory neurones in the sympathetic plexuses in 
the walls of the digestive tube. While it is impossible, by direct 
observation, to trace either sympathetic excitatory or sympa- 
thetic sensory elements back to their specific source in the cere- 
bro-spinal nervous system, indirect embryological and anatomical 
evidence warrants the conclusion that the sympathetic excita- 
tory neurones arise from cells which migrate from the neural tube 
along the fibers of the motor nerve-roots, while the sympathetic 
sensory neurones, wherever such neurones exist, arise from cells 
which migrate from the cerebro-spinal ganglia. This interpreta- 
tion makes the sympathetic neurones homologous with the affer- 
ent and the efferent components of the other functional divisions 
of the peripheral nervous system. 

8. Inasmuch as the cells migrating peripherally from the cere- 
bro-spinal nervous system are the ^indifferent" cells and the 
'^neuroblasts'" of Schaper, Schaper's conception of the develop- 
mental relations of the neurones and the supporting elements in 
the central nervous system, may be extended to the sympathetic 
neurones and the cells of the neurilemma. . 

9. The nervous system is a unit of which the sympathetic 
system is a part homologous with the other functional divisions. 
The sympathetic system may be looked upon as an accession to 
the nervous system, which has arisen comparatively late in the 
evolution of vertebrates in response to the conditions of the vegeta- 
tive life. 



SYMPATHETIC SYSTEM IN MAMMALS 255 

10. The fact that the sympathetic system is homologous 
with the other functional divisions of the nervous system lends a 
new aspect to the problems involving its functional relations. 
The fact that the vagal sympathetic plexuses have their origin in 
the hind-brain and the vagus ganglia will, doubtless, have an 
important bearing on certain physiological and psychological 
problems involving the heart action and the digestive functions. 



Accepted by the Wistar Institute of Anatomy and Biology, April 21, 1910. Printed July 8, 1910. 



256 ALBEKT ErXTZ 

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